Many successful pesticides and anti-nematode agents target ligand-gated ion channels (LGICs). Examples include dieldrin, which targets insect A-type gamma-aminobutyric acid receptors (GABAA receptors) (Ffrench-Constant R H, Rocheleau T A, Steichen J C, Chalmers A E (1993) A point mutation in a Drosophila GABA receptor confers insecticide resistance. Nature 363:449-451.), imidicloprid, which targets insect nicotinic acetylcholine receptors (nAChRs) (Zwart R, Oortgiesen M, Vijverberg H P M (1994) Nitromethylene heterocycles: selective agonists of nicotinic receptors in locust neurons compared to mouse N1E-115 and CBC3H1 cells. Pest Biochem Physiol 202-213.), levamisole, which targets nematode nAChRs (Fleming J T, Squire M D, Barnes T M, Tornoe C, Matsuda K, Ahnn J, Fire A, Sulston J E, Barnard E A, Sattelle D B, Lewis J A (1997) Caenorhabditis elegans levamisole resistance genes lev-1, unc-29, and unc-38 encode functional nicotinic acetylcholine receptor subunits. J Neurosci 17:5843-5857; Harrow I D, Gration K A F (1985) Mode of action of the anthelmintics morantel, pyrantel and levamisole on the muscle cell membrane of the nematode Ascaris suum. Pest Sci 16:662-672), and ivermectin, which targets nematode and insect glutamate-gated chloride channels (GluCls) (Cully D F, Paress P S, Liu K K, Schaeffer J M, Arena J P (1996) Identification of a Drosophila melanogaster glutamate-gated chloride channel sensitive to the antiparasitic agent avermectin. J Biol Chem 271:20187-20191. Cully D F, Vassilatis D K, Liu K K, Paress P S, Van der Ploeg L H, Schaeffer J M, Arena J P (1994) Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature 371:707-711.).
However, the evolution of resistance to pesticides and anti-nematode agents in exposed populations requires an ongoing search for new drug targets.